Process for producing 2-hydroxy-4-methyl-thiobutanoic acid

ABSTRACT

A process for producing 2-hydroxy-4-methylthiobutanoic acid is provided wherein 2-hydroxy-4-methylthiobutyronitrile is converted to 2-hydroxy-4-methylthiobutanamide by using sulfuric acid, then adding an aqueous solution containing ammonium bisulfate and ammonium sulfate to the reaction liquid to obtain an oil layer containing 2-hydroxy-4-methylthiobutanoic acid and an aqueous layer containing ammonium bisulfate and ammonium sulfate, then a part of the ammonium salts is separated from the aqueous layer, and the aqueous layer containing ammonium bisulfate and ammonium sulfate thus obtained is recycled as the aqueous solution containing ammonium bisulfate and ammonium sulfate described above. 
     According to the present invention, 2-hydroxy-4-methylthiobutanoic acid of high quality can be obtained without requiring organic solvents and with a greatly reduced amount of waste water.

TECHNICAL FIELD PERTINENT TO THE INVENTION

The present invention relates to a process for producing2-hydroxy-4-methylthiobutanoic acid, which is useful as a feed additiveand for other uses. In more particular, it relates to a process forproducing 2-hydroxy-4-methylthiobutanoic acid which permits a reductionof the amount of waste water produced and makes the use of organicsolvents unnecessary by recycling and reusing the aqueous solutioncontaining ammonium bisulfate and ammonium sulfate formed after thereaction of the process.

BACKGROUND OF THE INVENTION

A generally known process for producing 2-hydroxy-4-methylthiobutanoicacid comprises subjecting 2-hydroxy-4-methylthiobutyronitrile tohydration and successive hydrolysis by using sulfuric acid. A typicalmethod used for separating the intended 2-hydroxy-4-methylthiobutanoicacid from the reaction liquid resulting from the above-mentionedreaction includes a method comprising the use of an organic solvent,typically represented by methyl isobutyl ketone, as an extractionsolvent (see JP-B-7-97970).

However, the method which uses an organic solvent cannot be regarded asthe best one, because it requires the cost for solvent and increasedinvestment for equipment necessary for recovering the solvent, increasesload on environment, and moreover much care must be taken to avoid thecontamination of the final product by the solvent.

Another proposed method is a method comprising neutralizing the ammoniumbisulfate contained in the reaction liquid with ammonia to form ammoniumsulfate and then separating 2-hydroxy-4-methylthiobutanoic acid from theresulting reaction system by salting-out (see U.S. Pat. No. 4,912,257).This method, however, is not so advantageous, because it consumes largeammounts of sulfuric acid and ammonia.

To say the least, the above-mentioned methods are not preferable fromthe viewpoint of environmental friendliness, because they use a largeamount of sulfuric acid and produce a large amount of ammonium sulfateas a by-product.

On the other hand, a method has been proposed which comprises separatingammonium sulfate from the aqueous layer obtained by layer separationafter the reaction thereby to recover an aqueous ammonium bisulfatesolution, and recycling the aqueous solution to the reaction system (seeJapanese Patent Application No. 9-248592). This method is preferable inpoint of permitting reduction of the amount of sulfuric acid used,reduction of the amount of by-produced ammonium sulfate and reduction ofwaste water load. However, it is difficult to reduce environmental loadmarkedly by this method, because it uses an alcohol, such as methanol,for separating ammonium sulfate and ammonium bisulfate from each other.

SUMMARY AND OBJECTS OF THE INVENTION

The present inventors have made extensive study with the object ofproviding a process for producing 2-hydroxy-4-methylthiobutanoic acidwhich does not use organic solvents, such as methanol and methylisobutyl ketone, and moreover permits reduction of the amount ofammonium sulfate by-produced and of waste water load, which is theadvantage of the technique disclosed in Japanese Patent Application No.9-248592. As the result, it has been found that, in the process forproducing 2-hydroxy-4-methylthiobutanoic acid by using sulfuric acid,(1) addition of a mixed aqueous solution of ammonium bisulfate andammonium sulfate to the hydrolysis reaction system promotes thehydrolysis, (2) a layer separation phenomenon takes place rapidly afterthe above-mentioned reaction, (3) the oil layer obtained by the layerseparation can provide, through such operations as neutralization andfiltration, a 2-hydroxy-4-methylthiobutanoic acid product equivalent inquality to prior products, and (4) the aqueous layer obtained by thelayer separation can be recycled, through succeeding such operations ascrystallization and filtration, as a mixed aqueous solution used in (1)above. The present invention has been accomplished on the basis of theabove findings.

Thus, the present invention provides a process for producing2-hydroxy-4-methylthiobutanoic acid comprising the steps of:

(A) contacting an aqueous solution of2-hydroxy-4-methylthiobutyronitrile with sulfuric acid to obtain anaqueous solution containing 2-hydroxy-4-methylthiobutanoamide,

(B) adding an aqueous solution containing ammonium bisulfate andammonium sulfate to the solution obtained by step (A), to obtain anaqueous solution containing 2-hydroxy-4-methylthiobutanoic acid,

(C) allowing the aqueous solution obtained by step (B) to separate intotwo layers of an oil layer and an aqueous layer, and then separating theoil layer and the aqueous layer from each other,

(D) adding ammonia to the oil layer separated in step (C) to neutralizeat least part of the ammonium bisulfate in the oil layer to formcrystals of ammonium sulfate or crystals of sulfates including ammoniumsulfate and ammonium bisulfate, and thereafter removing the crystalsfrom the neutralized oil layer to obtain 2-hydroxy-4-methylthiobutanoicacid,

(E) cooling and/or concentrating the aqueous layer separated in step (C)to obtain an aqueous solution containing ammonium bisulfate and ammoniumsulfate as well as crystals of sulfates including ammonium sulfate andammonium bisulfate, and

(F) recycling all or part of the aqueous solution containing ammoniumbisulfate and ammonium sulfate obtained by step (E), to step (B) as theaqueous solution containing ammonium bisulfate and ammonium sulfate.

BRIEF DESCRIPTION OF DRAWING

FIG. 1 is a flow sheet showing one embodiment of the process of thepresent invention as a block diagram.

DETAILED DESCRIPTION OF THE INVENTION

In the process for producing 2-hydroxy-4-methylthiobutanoic acidaccording to the present invention, there are conducted step (A) ofcontacting an aqueous solution of 2-hydroxy-4-methylthiobutyronitrilewith sulfuric acid to obtain an aqueous solution containing2-hydroxy-4-methylthiobutanamide and step (B) of adding to the solutionthus obtained an aqueous solution containing ammonium bisulfate andammonium sulfate to obtain an aqueous solution containing2-hydroxy-4-methylthiobutanoic acid. According to the present invention,in the aqueous solution obtained in step (B), a layer separationphenomenon due to salting-out takes place rapidly.

In the present invention, following step (B), there is conducted step(C) of allowing the aqueous solution obtained by step (B) to separateinto two layers of an organic layer and an aqueous layer, and thenseparating the oil layer and the aqueous layer thus obtained from eachother. From the resulting oil layer are obtained2-hydroxy-4-methylthiobutanoic acid of high quality and crystals ofammonium sulfate or crystals of sulfates including ammonium sulfate andammonium bisulfate, in step (D), by adding ammonia (including aqueousammonia) to the oil layer to neutralize at least part of the ammoniumbisulfate in the oil layer to form ammonium sulfate, and then, throughsuch operations as concentrating the oil layer, depositing andseparating crystals of ammonium sulfate or crystals of sulfatesincluding ammonium sulfate and ammonium bisulfate from the oil layer.

From the aqueous layer obtained by the layer separation, crystalsincluding ammonium sulfate and ammonium bisulfate are deposited andseparated, in step (E), by an appropriate crystallizing operation, e.g.,concentration and/or cooling, and all or part of the aqueous solutioncontaining ammonium sulfate and ammonium bisulfate thus obtained isrecycled and used as the solution containing ammonium sulfate andammonium bisulfate used in step (B).

In the present invention, in producing 2-hydroxy-4-methylthiobutanoicacid by subjecting 2-hydroxy-4-methylthiobutyronitrile to hydration andsuccessive hydrolysis with sulfuric acid, an aqueous solution containingammonium bisulfate and ammonium sulfate is added at the time of thehydrolysis reaction, to utilize a layer separation due to salting-outwhich takes place after the reaction.

In the present invention, in step (A) in which an aqueous solution of2-hydroxy-4-methylthiobutyronitrile is contacted with sulfuric acid toeffect hydration, it is preferable to add the aqueous2-hydroxy-4-methylthiobutyronitrile solution by drops to sulfuric acid,whereby the hydration proceeds rapidly. The amount of sulfuric acid usedis usually about 0.5 to about 1.0 mole, preferably about 0.6 to about0.8 mole, relative to 1 mole of 2-hydroxy-4-methylthiobutyronitrile.When a 98% concentrated sulfuric acid is used, the water content of theaqueous solution of 2-hydroxy-4-methylthiobutyronitrile is preferablyabout 20-30% by weight. The sulfuric acid may also be used afterpreliminarily diluted with water. The reaction temperature is suitablyabout 40 to about 70° C. The reaction time is usually about 1-3 hoursincluding the time used for dropwise addition, though it variesdepending on the amount of sulfuric acid used.

In step (B), in which hydrolysis is conducted by adding an aqueoussolution containing ammonium bisulfate and ammonium sulfate, the aqueoussolution preferably contains an amount of water of about one time toabout two times the weight of sulfuric acid used for the hydration ofstep (A). The addition of ammonium bisulfate exerts an effect ofpromoting the hydrolysis, and it is suitable to add the ammonium sulfatein an amount so as not to cause deposition of salts, namely ammoniumsulfate, etc., in the aqueous solution to which the ammonium sulfate isadded and so as not to cause deposition of such salts when the reactionsystem is still maintained at the high temperature subsequent to thehydrolysis reaction. Ammonium sulfate, the addition of which has aneffect of greatly promoting spontaneous layer separation after thereaction, is used in the range of ammount of preferably about 0.1 toabout 0.7 time, more preferably about 0.4 to about 0.6 time the weightof ammonium bisulfate, because too much addition of the salt slows downthe progress of hydrolysis. When an aqueous solution containing ammoniumsulfate in an amount exceeding about 0.7 time is added, the completionof reaction sometimes becomes later than in adding water containing nosulfates.

The amount of the aqueous solution containing ammonium bisulfate andammonium sulfate used in step (B) is preferably such that the amount ofammonium sulfate in the aqueous solution might fall within the range ofabout 0.1 to about 0.4 mole relative to 1 mole of2-hydroxy-4-methylthiobutyronitrile.

The aqueous solution containing ammonium bisulfate and ammonium sulfateused in step (B) may contain components other than ammonium bisulfateand ammonium sulfate, for example, organic substances such as2-hydroxy-4-methylthiobutanoic acid, within the range which does notinhibit the hydrolysis or does not deteriorate the quality of the finalproduct.

Though the temperature of the hydrolysis reaction is not particularlylimited, it is preferably in the range of 90° C. to 130° C., because thehigher the reaction temperature, the easier the progress of thereaction. Since the boiling point of the reaction liquid at atmosphericpressure in the present system is about 115° C., the reaction ispreferably conducted in the neighborhood of the temperature. When ashorter reaction time is desired, the reaction may be conducted at ahigh temperature under an applied pressure by using a pressure-proofreaction apparatus.

Though the reaction time varies depending on the amounts of sulfuricacid and salts, such as ammonium sulfate, used, it is usually about 2hours to 5 hours.

The hydrolysis is usually conducted while stirring. After thehydrolysis, when the stirring is stopped and the reaction liquid isallowed to stand, the liquid separates into two layers of an oil layerand an aqueous layer (step (C)). The layer separation proceeds thefaster as the temperature is the higher; however, heating of the liquidis not always be needed since the layer separation is an operationsucceeding to the hydrolysis reaction, which is usually conducted at ahigh temperature. Depending on the amounts of salts, ammonium bisulfateand ammonium sulfate, used in step (B), the deposition of the saltspossibly occurs with the lowering of temperature of the reaction liquidand, therefore, sometimes the liquid may preferably be kept warm. Thevelocity of layer separation depends greatly on the amount of ammoniumsulfate, etc. and the water content of the system. The most simple anduseful method for promoting the progress of layer separation is toconcentrate the liquid.

The compositions of the oil layer and the aqueous layer are affected bythe amounts of ammonium bisulfate and ammonium sulfate, particularly theamount of ammonium sulfate, used at the time of hydrolysis. The higherthe content of ammonium sulfate in the system, the more2-hydroxy-4-methylthiobutanoic acid tends to be distributed to the oillayer side and the more sulfates tends to be distributed to the aqueouslayer side.

To the oil layer after layer separation is added ammonia to neutralizeat least part of ammonium bisulfate remaining in the oil layer intoammonium sulfate (step (D)). The amount of ammonia to be added ispreferably about 0.2 to about 3 times by mole relative to ammoniumbisulfate remaining in the oil layer. A more preferable amount ofammonia to be added depends on the water content of the intended2-hydroxy-4-methylthiobutanoic acid product. For example, when theproduct is to be obtained with a water content of about 4 to about 10%by weight, the amount of ammonia added is preferably about 1 to about 3times by mole relative to ammonium bisulfate remaining in the oil layer;when a product with a water content of less than about 4% by weight,more specifically about 3.5% by weight or less, particularly about 2% byweight or less is to be obtained, the amount of ammonia added ispreferably about 0.2 to about 1.4 times by mole relative to theremaining ammonium bisulfate.

The source of ammonia used may be any of the ammonia gas, liquid ammoniaand aqueous ammonia solution, but when a concentrating operation is doneafter neutralization, the use of ammonia gas or liquid ammonia isrecommendable.

From the slurry (ammonia-added layer) obtained after neutralization areseparated, through such operations as filtration or the like, crystalsof ammonium sulfate or crystals of sulfates including ammonium sulfateand ammonium bisulfate, whereby 2-hydroxy-4-methylthiobutanoic acid isobtained to form the objective product. When the separated crystals ofammonium sulfate and other salts contain an unnegligible amount of2-hydroxy-4-methylthiobutanoic acid, the 2-hydroxy-4-methylthiobutanoicacid contained may be recovered by washing the crystals of the saltswith an appropriate amount of water and then returning the washingfiltrate to the step of neutralizing the oil layer, or by mixing thecrystals of the salts into the aqueous layer obtained by layerseparation after the hydrolysis.

Further, concentration may be done before the separating operationconducted through filtration, etc., whereby the amount of ammoniumsulfate remaining in the obtained 2-hydroxy-4-methylthiobutanoic acidcan be reduced. For example, when the slurry is concentrated until itswater content reaches about 10% by weight or less relative to the liquidportion in the slurry, and thereafter subjected to separating operation,such as filtration, the content of ammonium sulfate in the ultimateproduct, calculated in terms of sulfate ion (SO₄ ²⁻ ion), can be reducedto 1% by weight or less without conducting any further operation. When ashorter filtration time is desired, it is most effective to raise thetemperature of the slurry.

When the amount of ammonia added to the oil layer and the water contentof the slurry before the separating operation are appropriatelycontrolled, 2-hydroxy-4-methylthiobutanoic acid of higher quality can beobtained. For example, a 2-hydroxy-4-methylthiobutanoic acid product canbe obtained which has a sulfate ion concentration in the product(determined after incorporating water thereinto so as to give a contentof 2-hydroxy-4-methylthiobutanoic acid therein, measured bypotentiometric titration, of about 89% by weight) of not higher than 1%by weight, has a kinematic viscosity of not higher than 90 cSt and henceis excellent in ease of handling.

When the amount of ammonia used for neutralization is too small, theconcentration of sulfate ions contained in the product tends to be toohigh; on the other hand, when ammonia is added in excess, the kinematicviscosity of the product is sometimes too high. When the water contentof the slurry before the separating operation is high, both the sulfateion concentration in the product and the kinematic viscosity tend to behigh. Therefore, when it is desired to obtain a product having both alow kinematic viscosity and a low sulfate ion concentration, it isadvisable to conduct neutralization with an appropriate, small amount ofammonia and thereafter to distill off much of water from the slurry inthe concentrating operation.

For example, a specific 2-hydroxy-4-methylthiobutanoic acid product canbe obtained when ammonia is added to the oil layer in an amount of about0.2 to about 1.4 molar equivalents relative to the ammonium bisulfatecontained in the oil layer obtained after layer separation, then theslurry is concentrated until the water content of the slurry reaches3.5% by weight or less relative to the liquid portion in the slurry, andthereafter the slurry is subjected to a separating operation withoutconducting any additional operation. The product has a sulfate ion (SO₄²⁻ ion) concentration therein of not higher than about 1% by weight anda kinematic viscosity of not higher than about 90 cSt (as determinedafter incorporating water thereinto so as to give a content of2-hydroxy-4-methylthiobutanoic acid therein, measured by polentiometrictitration, of about 89% by weight).

In order that the neutralization be controlled in a simple and easy way,it may be controlled by using a pH value. In such a case,2-hydroxy-4-methylthiobutanoic acid with the above-mentioned highquality can be obtained by adding ammonia so as to give a pH of the oillayer at 25° C. in the range of about 0.4 to about 2. The operation ofneutralization may also be conducted at high temperatures, and thecontrol may be conducted with a pH value measured at high temperatures.

Further, another specific 2-hydroxy-4-methylthiobutanoic acid productcan be obtained, when ammonia is added to the slurry in an amount ofabout 0.2 to about 1.4 molar equivalents relative to ammonium bisulfatecontained in the oil layer obtained after layer separation (or ammoniais added until the pH of the oil layer at 25° C. becomes between about0.4 and about 2), then the slurry is concentrated until the watercontent thereof reaches about 2% by weight or less relative to theliquid portion in the slurry and thereafter the slurry is subjected to aseparating operation, without conducting any additional operation. Theproduct has a sulfate ion concentration therein of not higher than about1% by weight and a kinematic viscosity of not higher than 80 cSt (asdetermined after incorporating water thereinto so as to give a contentof 2-hydroxy-4-methylthiobutanoic acid therein, measured bypotentiometric titration, of about 89% by weight).

In the present invention, by concentrating and/or cooling the aqueouslayer obtained by layer separation and then conducting such operationsas filtration, etc., salts comprising ammonium bisulfate and ammoniumsulfate are separated as deposits and an aqueous solution containingammonium bisulfate and ammonium sulfate is obtained (step (E)). Theaqueous solution obtained above further contains2-hydroxy-4-methylthiobutanoic acid. A part or the whole of thesolution, as it is or after its water content has been adjusted, isutilized as the aqueous solution added in the hydrolysis reaction instep (B) (step (F)). The ratio of ammonium bisulfate to ammonium sulfatein the aqueous solution can be varied by controlling the crystallizationconditions of concentration and/or cooling in obtaining theabove-mentioned deposits of salts of ammonium sulfate, etc. The optimumconditions for the crystallization depend greatly on the composition ofthe salts of ammonium sulfate, etc. in the aqueous layer. Therefore,when the salts are deposited by cooling for example, it is advisable todetermine appropriate crystallization conditions by preliminarilypreparing the solubility curves of ammonium sulfate and ammoniumbisulfate in the aqueous layer actually obtained, and then assuming acooling temperature and estimating the salt composition of the filtrateobtained at the temperature.

Since the crystals of the salts thus obtained comprise a mixture ofammonium bisulfate and ammonium sulfate, when it is desired to recoverthem as ammonium sulfate, the recovery is preferably effected byneutralizing them with ammonia. The ammonia used may be in any of theforms of ammonia gas, liquid ammonia and aqueous ammonia solution. Whenthe crystals contain a small amount of 2-hydroxy-4-methylthiobutanoicacid, it is preferable to contact an aqueous ammonia solution with thecrystals to serve both for neutralization and washing and then tosubject the resulting product to separating operations such asfiltration, etc., whereby 2-hydroxy-4-methylthiobutanoic acid isrecovered on the liquid side.

Such a neutralizing operation with ammonia may also be conducted aftercombining the above-mentioned salt crystals with the ammonium sulfateand other salts which have developed in other steps, for example,ammonium sulfate, etc. separated from the slurry obtained afterneutralization of the oil layer. In such a way, salts of ammoniumsulfate, etc. developed in plural spots can be handled together.

The ammonium sulfate obtained through such a neutralizing operationcontains a small amount of 2-hydroxy-4-methylthiobutanoic acid. When anaqueous solution of the ammonium sulfate is contacted with active carbonand then subjected to such operations as crystallization, etc., a highquality, crystalline ammonium sulfate can be obtained as a by-product.In the case, 2-hydroxy-4-methylthiobutanoic acid is adsorbed to theactive carbon; this not only prevents the accumulation of2-hydroxy-4-methylthiobutanoic acid in the ammonium sulfate recoverysystem but also permits the removal of odor components, such assulfides. It is needless to say that similar effects can also beexpected when active carbon is contacted with the salts beforeneutralization with ammonia, namely in the state of a mixed aqueoussolution of ammonium sulfate and ammonium bisulfate.

One embodiment of the present invention is described below withreference to a flow sheet (FIG. 1) shown in the form of block diagram.

First, concentrated sulfuric acid is placed in a reaction vessel and2-hydroxy-4-methylthiobutyronitrile is added by drops thereto. Aftercompletion of the dropwise addition, the resulting mixture is held for1-2 hours to effect hydration. The liquid temperature during the time is40-70° C. Then, an aqueous solution containing ammonium bisulfate andammonium sulfate obtained by the method described below is added, theresulting mixture is heated to 115° C. and held for 2-5 hours to effecta hydrolysis reaction.

Then the reaction liquid is allowed to stand and to separate into twolayers, and the oil layer and the aqueous layer thus formed areseparated from each other.

To the oil layer is added ammonia to neutralize ammonium bisulfatedissolving in the layer into ammonium sulfate, to obtain a slurry. Thenthe slurry is concentrated until the water content of the slurry reaches10% by weight or less, preferably 3% by weight or less, more preferably2% by weight or less, and then ammonium sulfate is removed byfiltration, leaving behind a filtrate containing2-hydroxy-4-methylthiobutanoic acid product.

The aqueous layer is subjected to a crystallizing operation by coolingand/or concentration and then filtered to separate the depositedammonium bisulfate and ammonium sulfate, leaving behind an aqueoussolution containing ammonium sulfate, ammonium bisulfate and2-hydroxy-4-methylthiobutanoic acid as a filtrate. The aqueous solutionis, after its water content has been adjusted, recycled and used as theaqueous solution to be added at the time of hydrolysis.

The deposited salt obtained in the above-mentioned filtration containsammonium bisulfate. Therefore, when effective utilization thereof asammonium sulfate is desired, it is neutralized with ammonia to recoverthe whole as ammonium sulfate. Further, the deposited salt contains some2-hydroxy-4-methylthiobutanoic acid adhereing thereto. The acid can berecovered by washing the salt with water after neutralization withammonia or by washing the salt with an aqueous ammonia solution, whichserves both for neutralization and washing.

As set forth above, according to the process of the present invention,in producing 2-hydroxy-4-methylthiobutanoic acid,

(1) addition of an aqueous solution containing ammonium bisulfate andammonium sulfate to the step of hydrolysis of2-hydroxy-4-methylthiobutanamide promotes the layer separation of thereaction liquid containing 2-hydroxy-4-methylthiobutanoic acid formed byhydrolysis into two layers, an oil layer and an aqueous layer, whereby ahigh quality 2-hydroxy-4-methylthiobutanoic acid can be separatedwithout requiring organic solvents, and

(2) the aqueous layer obtained by the layer separation can be recycled,after a simple operation, to the reaction system as an aqueous solutionof ammonium bisulfate and ammonium sulfate.

Accordingly, the present invention makes it possible to constitute aprocess which requires no organic solvent and imposes very little wastewater load. Thus, the invention is of great industrial value not only inthe reduction of production cost but also from its environmentalfriendliness.

EXAMPLES

The process of the present invention is described in detail below withreference to Examples, but it is not limited thereto.

Example 1

To 196.8 g (1.4 moles) of a 70% aqueous sulfuric acid solution was addedby drops, while stirring, 294.1 g (2.0 moles) of an 89.2% aqueous2-hydroxy-4-methylthiobutyronitrile solution over 30 minutes. The innertemperature of the reaction mixture during the above dropwise additionwas controlled so as to be about 50° C. After completion of the dropwiseaddition, the resulting mixture was stirred for further two hours whilethe inner temperature being kept at 50° C., to effect hydration.

To the resulting mixture were then added each of

(a) 228.7 g of water,

(b) a solution of 94.0 g of ammonium bisulfate dissolved in 228.7 g ofwater,

(c) a solution of 94.0 g ammonium bisulfate and 39.6 g of ammoniumsulfate dissolved in 228.7 g of water,

(d) a solution of 94.0 of ammonium bisulfate and 52.8 g of ammoniumsulfate dissolved in 228.7 g of water, and

(e) a solution of 94.0 g of ammonium bisulfate and 79.3 g of ammoniumsulfate dissolved in 228.7 g of water. The resulting mixtures were heldat 115° C. while stirring, to effect hydrolysis. The changes in thehydrolysis with the lapse of time (elapsed from the addition of thesolutions described in (a) to (e) above) are shown in Table 1 in termsof conversion to 2-hydroxy-4-methylthiobutanoamide. The analysis wasmade by liquid chromatography.

TABLE 1 Solution used for hydrolysis 1 hr 2 hr 3 hr 4 hr 5 hr (a) 97.16%99.24% 99.79% 99.89% 99.93% (b) 99.16% 99.91% 99.97% 100% 100% (c)99.57% — 99.88% — 99.98% (d) — — 99.83% — 99.94% (e) 93.92% 98.36%99.52% 99.76% 99.93%

Example 2

Each of the mixtures after the hydrolysis effected by the addition of(a) to (e) of Example 1 was allowed to stand and to separate into twolayers. Then the mixtures were kept at 70° C. and allowed to stand torespectively separate an oil layer and an aqueous layer from each other.Then the respective layers were analyzed for their respective contentsof 2-hydroxy-4-methylthiobutanoic acid (abbreviated as HMBA in Tables),ammonium bisulfate and ammonium sulfate. The results obtained are shownin Table 2 for the oil layer and in Table 3 for the aqueous layer.

The component analysis of the oil layer and the aqueous layer wasconducted by liquid chromatography for 2-hydroxy-4-methylthiobutanoicacid and by ion chromatography for ammonium bisulfate and ammoniumsulfate. The units are all in mole.

TABLE 2 Components of oil layer Solution used Ammonium Ammonium forhydrolysis HMBA bisulfate sulfate (a) No oil-water separation (b) 1.7140.532 0.244 (c) 1.790 0.335 0.168 (d) 1.850 0.277 0.189 (e) 1.868 0.2020.193

TABLE 3 Components of aqueous layer Solution used Ammonium Ammonium forhydrolysis HMBA bisulfate sulfate (a) No oil-water separation (b) 0.2461.049 0.372 (c) 0.159 1.235 0.738 (d) 0.141 1.214 0.863 (e) 0.121 1.2561.082

Example 3

The ammonium bisulfate in the oil layer (456.1 g) obtained in (c) ofExample 2 was neutralized with a sufficient amount of an 25% aqueousammonia solution (45 g). The resulting liquid was divided into 6portions. Each portion was concentrated to the concentrating rate shownin Table 4, then cooled to room temperature and filtered to obtain2-hydroxy-4-methylthiobutanoic acid product as the filtrate. The watercontent and the sulfate ion concentration in the product obtained ateach concentration rate are shown in Table 4.

The sulfate ion concentration was determined by using ion chromatographyand the water content by using a moisture meter by Karl Fischer'smethod.

TABLE 4 100% Concentra- (Not con- tion rate centrated 86% 84% 82% 80%76% Water 24.5% 14.0% 12.7% 10.4%  8.5%  3.3% content Sulfate  6.2% 1.8%  1.4% 0.95% 0.62% 0.23% ion

Example 4

The following operations {circle around (1)}-{circle around (4)} wereconducted.

{circle around (1)} To 96.6 g (0.7 mole) of 71% sulfuric acid was addedby drops 148 g (1.0 mole) of an 88.7% aqueous2-hydroxy-4-methylthiobutyronitrile solution over 30 minutes whilestirring and the resulting mixture was thereafter held while stirringfor 90 minutes.

{circle around (2)} An aqueous sulfate solution was prepared by using 70g (0.6 mole) of ammonium bisulfate, 33 g (0.25 mole) of ammonium sulfateand 114 g of water. The solution was added to the reaction mixtureobtained in {circle around (1)} above, and the resulting mixture wasallowed to react at 115° C. for 4 hours. The mixture after the reactionwas allowed to stand and to separate into two layers (an oil layer andan aqueous layer), and the layers were separated from each other.

{circle around (3)} To the oil layer obtained in {circle around (2)}above was added 13.6 g (0.2 mole) of a 25% aqueous ammonia solution, andthe resulting mixture was concentrated until the water content of theoil layer reached 10% or less relative to the liquid portion in themixture. Thereafter, by filtration, 2-hydroxy-4-methylthiobutanoic acidproduct was obtained in the filtrate and ammonium sulfate in the cake.

{circle around (4)} The aqueous layer obtained in {circle around (2)}above was cooled to 30° C., and the deposited ammonium sulfate wasseparated by filtration. About 5 to about 10% of the filtrate wasdischarged out of the system so that the composition and the amount ofsulfates in the filtrate might be constant. Then water was added to theremaining filtrate so that the amount of water in the filtrate mightbecome 114 g, thereby to prepare an aqueous sulfate solution.

In the same manner as described above except for using the aqueoussulfate solution prepared in {circle around (4)} above in place of theaqueous solution prepared in {circle around (2)} by using ammoniumbisulfate and ammonium sulfate, the operations of {circle around (1)} to{circle around (4)} described above were repeated 3 times.

Table 5 shows the content of 2-hydroxy-4-methylthiobutanoic acid(including its dimer; unit:mole) 5 in the oil layer and aqueous layer,the content being determined for each of the above-mentioned 4times-repeated experiments. The analysis was made by liquidchromatography.

TABLE 5 Number of time of experiment In oil layer In aqueous layer 1sttime 0.926 0.073 2nd time 0.945 0.078 3rd time 0.968 0.070 4th time0.943 0.072

Table 6 shows the ratio of ammonium bisulfate (mole) to ammonium sulfate(mole) in the aqueous sulfate solution added in {circle around (2)}, theratio of ammonium bisulfate (mole) to ammonium sulfate (mole) in theaqueous layer obtained in {circle around (2)}, and the ratio of ammoniumbisulfate (mole) to ammonium sulfate (mole) in the sulfates crystalsseparated from the aqueous layer in {circle around (4)}. The analysiswas made by a combination of neutralization titration using NaOH and ionchromatography.

TABLE 6 Composition * of Composition * aqueous layer Aqueous of sulfatesobtained in {circle around (2)} layer obtained in {circle around (4)}1st time 0.600/0.250 — 0.205/0.186 2nd time 0.605/0.269 0.879/0.5000.198/0.186 3rd time 0.608/0.270 0.862/0.506 0.228/0.200 4th time0.606/0.267 0.902/0.514 0.205/0.187 Note: *: molar ratio of ammoniumbisulfate/ammonium sulfate

The results shown in Tables 5 and 6 reveal that the compositions of theoil layer and the aqueous layer obtained after the reaction and thecompositions of the aqueous sulfate solution and the sulfate crystalsseparated from the aqueous layer by crystallization are constant andsteady through the experiments.

Table 7 shows the composition of the product obtained in the experimentsrepeated 4 times. 2-Hydroxy-4-methylthiobutanoic acid and its dimer wereanalyzed by liquid chromatography, the sulfate ion by ionchromatography, and the water content by a moisture meter by KarlFischer's method. The color was expressed by the Gardner color scale.

TABLE 7 HMBA Sulfate Water HMBA dimer ion content Color 1st time 76.19%15.26% 0.38% 6% 13 2nd time 75.54% 14.66% 0.62% 7% 13 3rd time 74.58%15.08% 0.59% 8% 13 4th time 68.77% 13.55% 1.65% 14%  13

The results obtained above show that products with approximatelyconstant composition were obtained, although the sulfate ion content inthe product was high only in the 4th time operation because theconcentration in operation {circle around (3)} was insufficient at thattime.

Example 5

The following operations {circle around (1)}-{circle around (8)} wereconducted as the experiment of the first time.

{circle around (1)} To 197.9 g (1.4 moles) of a 69.3% aqueous sulfuricacid solution was added by drops, while stirring, 293 g (2.0 moles) ofan 89.6% aqueous 2-hydroxy-4-methylthiobutyronitrile solution over 30minutes, and the resulting mixture was held while stirring for further90 minutes.

{circle around (2)} An aqueous sulfate solution was prepared by using140 g (1.2 moles) of ammonium bisulfate, 66 g (0.5 mole) of ammoniumsulfate and 228 g of water. The solution was added to the reactionmixture obtained in {circle around (1)} above, and the resulting mixturewas allowed to react at 115° C. for 4 hours. The mixture after thereaction was allowed to stand and to separate into two layers, and thelayers were separated from each other.

{circle around (3)} To the oil layer thus obtained were added thewashing filtrate obtained in {circle around (4)} (which, however, wasnot used in the first time of experiment) and 20 g of a 25% aqueousammonia solution, and the resulting mixture was concentrated underreduced pressure until the water content of the oil layer reached 10% orless relative to the liquid portion in the oil layer. Thereafter, byfiltration, the objective product was obtained in the filtrate andammonium sulfate crystals in the deposit.

{circle around (4)} The ammonium sulfate obtained in {circle around (3)}was washed with 30 g of water and filtered to obtain ammonium sulfateand a washing filtrate.

{circle around (5)} The aqueous layer was cooled to 25° C. and then thedeposited ammonium sulfate was separated by filtration. Then, from 0 toabout 10% of the filtrate was discharged out of the system so that thecomposition and the amount of the sulfates in the filtrate might beconstant. Then, water was added to the remaining filtrate so that theamount of water in the filtrate might become 228 g, thereby the preparean aqueous sulfate solution.

{circle around (6)} Parts of the ammonium sulfate and the filtrateformed in {circle around (4)} and {circle around (5)} were dissolved in300-400 g of water. To this solution were added the filtrate obtained in{circle around (8)} (which, however, was not used in the first time ofexperiment) and 30-40 g of a 25% aqueous ammonia solution, to obtain anaqueous ammonium sulfate solution.

{circle around (7)} To the aqueous ammonium sulfate solution obtained in{circle around (6)} was added 6-7 g (corresponding to 1% by weight ofthe aqueous solution) of active carbon. The resulting mixture wasstirred at room temperature for one hour and then filtered.

{circle around (8)} The filtrate obtained in {circle around (7)} wasconcentrated under reduced pressure until a concentration rate of 40%was reached, and then filtered at room temperature to obtain ammoniumsulfate crystals.

In the same manner as described above except for using the aqueoussulfate solution prepared in {circle around (5)} in place of the aqueoussolution prepared in {circle around (2)} by using ammonium bisulfate andammonium sulfate, the operations of {circle around (1)}-{circle around(1)} described above were repeated 5 times.

Table 8 shows the amount of the product obtained, the yield, and thecontent of 2-hydroxy-4-methylthiobutanoic acid (including the dimer,unit: mole) in the operation {circle around (3)} of each experiment inthe above-mentioned experiments repeated 6 times. The analysis was madeby liquid chromatography.

TABLE 8 Amount obtained HMBA content Yield 1st time 237.2 g 98.6% 79.0%2nd time 323.5 g 92.8% 99.9% 3rd time 304.7 g 93.5% 94.9% 4th time 292.8g 92.3% 90.0% 5th time 328.1 g 90.6% 99.0% 6th time 312.3 g 97.5%101.4% 

In Table 8, the yields at the first time and the fourth time are low. Asfor the first time, this is because 2-hydroxy-4-methylthiobutanoic acidadhering to the sulfate crystals obtained in the filtration conductedafter concentration of the oil layer was carried over on and after thesecond time. As for the fourth time, this is because the filtration timewas set shorter than in other times of experiment and hence more2-hydroxy-4-methylthiobutanoic acid was adhered to the sulfate crystals.Anyhow, since almost all of the adhering HMBA is recovered on and afterthe next time, the average yield on and after the second time ofexperiment is as high as 97% or more.

Table 9 shows the amount of the washing filtrate obtained in {circlearound (4)} and the content of 2-hydroxy-4-methylthiobutanoic acid(including the dimer; mole) in the washing filtrate, in theabove-mentioned experiments repeated 6 times.

TABLE 9 Amount of washing filtrate HMBA 1st time 142.2 g 0.21 mole 2ndtime 145.9 g 0.15 mole 3rd time 120.2 g 0.18 mole 4th time 158.0 g 0.36mole 5th time 187.4 g 0.27 mole 6th time 186.9 g 0.24 mole

Table 10 shows the composition (in mole) of the aqueous sulfate solutionprepared in {circle around (5)} (the solution used in {circle around(2)} of the next experiment), in the above-mentioned experimentsrepeated 6 times. The respective sulfates were analyzed by ionchromatography.

TABLE 10 Ammonium Ammonium bisulfate sulfate HMBA 1st time 1.200 moles0.500 mole — 2nd time 1.316 moles 0.549 mole 0.14 mole 3rd time 1.221moles 0.581 mole 0.09 mole 4th time 1.188 moles 0.500 mole 0.09 mole 5thtime 1.277 moles 0.590 mole 0.10 mole 6th time 1.190 moles 0.419 mole0.10 mole

Table 11 shows the content of 2-hydroxy-4-methylthiobutanoic acid(including the dimer; mole) in the aqueous ammonium sulfate solutionobtained in {circle around (6)} and the amount of2-hydroxy-4-methylthiobutanoic acid (including the dimer; mole)contained in the solution obtained after the active carbon treatment of{circle around (7)}, in the above-mentioned experiments repeated 6times.

TABLE 11 Aqueous solution Aqueous solution obtained in {circle around(6)} obtained in {circle around (7)} (Before active (After active carbontreatment) carbon treatment) 1st time 0.026 mole 0.008 mole 2nd time0.016 mole 0.006 mole 3rd time 0.018 mole 0.006 mole 4th time 0.010 mole0.004 mole 5th time 0.048 mole 0.014 mole 6th time 0.018 mole 0.006 mole

Table 11

Table 12 shows the concentration of the odor components (dimethylsulfide, dimethyl disulfide) in the ammonium sulfate crystals obtainedin {circle around (8)}, in the above-mentioned experiments repeated 6times. The odor components were analyzed by head space gaschromatography.

TABLE 12 Dimethyl sulfide Dimethyl disulfide 1st time 0.04 ppm 0.02 ppm2nd time 0.04 ppm ≧0.01 ppm   3rd time ≧0.01 ppm   ≧0.01 ppm   4th time≧0.01 ppm   0.03 ppm 5th time 0.08 ppm 0.04 ppm 6th time Not determinedNot determined No active carbon 0.20 ppm 0.10 ppm treatment

Example 6

The same operations as {circle around (1)} and {circle around (2)} ofExample 4 were conducted to obtain an oil layer, which was thenneutralized with 0-8.6 g of a 25% aqueous ammonia solution(corresponding to 0-1.2 molar equivalents relative to the ammoniumbisulfate used in {circle around (8)}, and water was distilled off withan evaporator. The resulting slurry was filtered at 70° C., and thefiltrate was measured for its water content and the content of2-hydroxy-4-methylthiobutanoic acid.

Then, water was added to the filtrate so that the content of2-hydroxy-4-methylthiobutanoic acid therein might become 89.0% byweight, thereby to prepare the product.

The content of 2-hydroxy-4-methylthiobutanoic acid was determined bypotentiometric titration, the water content by the Karl Fischer'smethod, the sulfate ion by ion chromatography and the kinematicviscosity by a Cannon-Fenske viscometer at 25° C.

Table 13 shows the amount of ammonia, the pH of the oil layer at 25° C.,the water content (% by weight) of the filtrate, the sulfate ionconcentration (% by weight) in the product and the kinematic viscosity(cSt) thus determined.

TABLE 13 Oil Water content Sulfate ion Kinematic Ammonia layer pH offiltrate concentra- viscosity amount* (25° C.) (wt %) tion (wt %) (cSt)0   0.2  0.63 2.04 — 0   0.2  1.63 2.32 — 0.1 0.36 0.57 0.91 — 0.1 0.361.85 1.17 — 0.1 0.36 2.60 1.43 — 0.2 0.41 0.90 0.52 66.5 0.2 0.41 2.300.76 74.3 0.2 0.41 2.90 0.86 80.0 0.3 0.59 0.70 0.43 73.5 0.3 0.59 1.700.58 77.1 0.3 0.59 2.50 0.69 78.1 0.4 0.65 1.20 0.61 73.3 0.4 0.65 2.200.75 78.6 0.4 0.65 3.10 0.97 80.5 0.7 0.88 1.10 0.60 73.8 0.7 0.88 1.990.73 78.3 0.7 0.88 2.91 0.87 81.9 0.7 0.88 3.88 1.09 84.8 0.8 0.99 0.900.54 74.7 0.8 0.99 1.94 0.71 78.6 0.8 0.99 3.08 0.85 79.1 0.8 0.99 3.921.04 80.0 0.9 1.10 0.80 0.53 72.8 0.9 1.10 2.03 0.70 80.3 0.9 1.10 2.640.80 79.1 0.9 1.10 3.58 1.02 88.9 1.0 1.27 1.00 0.54 70.9 1.0 1.27 2.090.70 74.5 1.0 1.27 2.85 0.85 78.6 1.0 1.27 3.72 0.99 84.4 1.0 1.27 4.671.31 — 1.1 1.53 0.66 0.57 69.4 1.1 1.53 1.66 0.73 74.0 1.1 1.53 2.860.89 80.7 1.2 1.73 0.81 0.40 69.7 1.2 1.73 1.99 0.55 76.2 1.2 1.73 3.340.65 78.6 Note: *Unit is molar equivalent relative to ammonium bisulfatein oil layer —: Not determined

What is claimed is:
 1. A process for producing2-hydroxy-4-methylthiobutanoic acid comprising the steps of: (A)contacting an aqueous solution of 2-hydroxy-4-methylthiobutyronitrilewith sulfuric acid to obtain an aqueous solution containing2-hydroxy-4-methylthiobutanamide, (B) adding an aqueous solutioncontaining ammonium bisulfate and ammonium sulfate to the solutionobtained by step (A) to obtain an aqueous solution containing2-hydroxy-4-methylthiobutanoic acid, (C) allowing the aqueous solutionobtained by step (B) to separate into two layers of an oil layer and anaqueous layer, and then separating the oil layer and the aqueous layerfrom each other, (D) adding ammonia to the oil layer separated in step(C) to neutralize at least part of the ammonium bisulfate in the oillayer to form crystals of ammonium sulfate or crystals of sulfatesincluding ammonium sulfate and ammonium bisulfate, and thereafterremoving the crystals from the neutralized oil layer to obtain2-hydroxy-4-methylthiobutanoic acid, (E) cooling and/or concentratingthe aqueous layer separated in step (C) to obtain an aqueous solutioncontaining ammonium bisulfate and ammonium sulfate as well as crystalsof sulfates including ammonium sulfate and ammonium bisulfate, and (F)recycling all or part of the aqueous solution containing ammoniumbisulfate and ammonium sulfate obtained by step (E), to step (B) as theaqueous solution containing ammonium bisulfate and ammonium sulfate. 2.The process according to claim 1, wherein in step (A) the sulfuric acidis used in an amount of from 0.6 to 0.8 molar equivalent relative to2-hydroxy-4-methylthiobutyronitrile.
 3. The process according to claim1, wherein the aqueous solution containing ammonium bisulfate andammonium sulfate in step (B) contains ammonium sulfate in an amount 0.1to 0.7 times that of ammonium bisulfate in weight basis.
 4. The processaccording to claim 1, wherein step (E) further includes the step ofneutralizing the crystals of sulfates including ammonium sulfate andammonium bisulfate with ammonia to recover the sulfates as ammoniumsulfate.
 5. The process according to claim 1, wherein step (D) furtherincludes the step of washing the crystals of ammonium sulfate or thecrystals of sulfates including ammonium sulfate and ammonium bisulfatewith water and using all or part of the washings for the neutralizationin step (D).
 6. The process according to claim 1, which furthercomprises the step of: (G) dissolving all or part of the ammoniumsulfate and/or the ammonium bisulfate obtained in any one, two or threeof steps (D), (E) and (F) in water and neutralizing the resultingsolution with ammonia to obtain an aqueous solution of ammonium sulfate.7. The process according to claim 6, wherein step (G) further includesthe step of contacting all or part of the aqueous solution of ammoniumsulfate with active carbon.
 8. The process according to claim 1, whereinin step (D) the ammonia is added to the oil layer in an amount of about0.2 to about 3 molar equivalents relative to the ammonium bisulfate inthe oil layer, and then the ammonia-added layer is concentrated untilthe layer contains 10% by weight or less of water relative to a liquidportion in the layer.
 9. The process according to claim 1, wherein instep (D) the ammonia is added to the oil layer so that the resultinglayer has a pH falling within the range of from 0.4 to 2.0 at 25° C.,and then the ammonia-added layer is concentrated until the ammonia-addedlayer contains about 3.5% by weight or less of water relative to aliquid portion in the ammonia-added layer.
 10. The process according toclaim 9, wherein the ammonia-added layer is concentrated until theammonia-added layer contains about 2% by weight or less of waterrelative to a liquid portion in the ammonia-added layer.
 11. The processaccording to claim 1, wherein in step (D) the ammonia is added to theoil layer in an amount of from about 1 to about 3 molar equivalentsrelative to the ammonium bisulfate in the oil layer, and then theammonia-added layer is concentrated until the ammonia-added layercontains about 4 to about 10% by weight of water relative to a liquidportion in the ammonia-added layer.
 12. The process according to claim1, wherein in step (D) the ammonia is added to the oil layer in anamount of from about 0.2 to about 1.4 molar equivalents relative to theammonium bisulfate in the oil layer, and then the ammonia-added layer isconcentrated until the ammonia-added layer contains about 3.5% by weightor less of water relative to a liquid portion in the ammonia-addedlayer.
 13. The process according to claim 1, wherein in step (D) theammonia is added to the oil layer in an amount of from 0.2 to 1.4 molarequivalents relative to the ammonium bisulfate in the oil layer, andthen the ammonia-added layer is concentrated until the ammonia-addedlayer contains about 2% by weight or less of water relative to a liquidportion in the ammonia-added layer.
 14. The process according to claim1, wherein the removal of the crystals from the oil layer in step (D) isconducted at a temperature of about 40° C. or above.